rs12728401

Variant names:

• chr1-3815401-G-A
• rs12728401
• NM_014704.4:c.*1C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-3815401-G-A
• chr1-3815401-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014704.4(CEP104):​c.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,603,542 control chromosomes in the GnomAD database, including 13,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1339 hom., cov: 34)
  • Exomes 𝑓: 0.13 (12184 hom.)
• Consequence: CEP104 NM_014704.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01
• Publications: 8 publications found

Genes affected

CEP104 (HGNC:24866): (centrosomal protein 104) This gene encodes a centrosomal protein required for ciliogenesis and for ciliary tip structural integrity. The mammalian protein contains three amino-terminal hydrophobic domains, two glycosylation sites, four cysteine-rich motifs, and two regions with homology to the glutamate receptor ionotropic, NMDA 1 protein. During ciliogenesis, the encoded protein translocates from the distal tips of the centrioles to the tip of the elongating cilium. Knockdown of the protein in human retinal pigment cells results in severe defects in ciliogenesis with structural deformities at the ciliary tips. Allelic variants of this gene are associated with the autosomal-recessive disorder Joubert syndrome, which is characterized by a distinctive mid-hindbrain and cerebellar malformation, oculomotor apraxia, irregular breathing, developmental delay, and ataxia. [provided by RefSeq, Feb 2016]

CEP104 Gene-Disease associations (from GenCC):

• Joubert syndrome 25

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-3815401-G-A is Benign according to our data. Variant chr1-3815401-G-A is described in ClinVar as [Benign]. Clinvar id is 1241222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP104	NM_014704.4	c.*1C>T		3_prime_UTR_variant	Exon 22 of 22	ENST00000378230.8	NP_055519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP104	ENST00000378230.8	c.*1C>T		3_prime_UTR_variant	Exon 22 of 22	5	NM_014704.4	ENSP00000367476.3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19612 AN: 152186 Hom.: 1340 Cov.: 34

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.117 AC: 28454 AN: 242360 AF XY: 0.118

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.0640

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.0427

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.127 AC: 183806 AN: 1451238 Hom.: 12184 Cov.: 30 AF XY: 0.126 AC XY: 91161 AN XY: 721976

African (AFR) AF: 0.141 AC: 4699 AN: 33350

American (AMR) AF: 0.0677 AC: 2997 AN: 44278

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5375 AN: 25940

East Asian (EAS) AF: 0.0479 AC: 1896 AN: 39614

South Asian (SAS) AF: 0.102 AC: 8720 AN: 85254

European-Finnish (FIN) AF: 0.154 AC: 7851 AN: 50908

Middle Eastern (MID) AF: 0.146 AC: 841 AN: 5746

European-Non Finnish (NFE) AF: 0.130 AC: 143567 AN: 1106026

Other (OTH) AF: 0.131 AC: 7860 AN: 60122

GnomAD4 genome AF: 0.129 AC: 19633 AN: 152304 Hom.: 1339 Cov.: 34 AF XY: 0.128 AC XY: 9525 AN XY: 74486

African (AFR) AF: 0.137 AC: 5697 AN: 41572

American (AMR) AF: 0.0983 AC: 1504 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3470

East Asian (EAS) AF: 0.0473 AC: 245 AN: 5182

South Asian (SAS) AF: 0.0940 AC: 454 AN: 4832

European-Finnish (FIN) AF: 0.157 AC: 1671 AN: 10620

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8966 AN: 68008

Other (OTH) AF: 0.127 AC: 269 AN: 2114

Alfa AF: 0.112 Hom.: 396

Bravo AF: 0.127

Asia WGS AF: 0.0720 AC: 255 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.83
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12728401; hg19: chr1-3731965;